1. Field of the Invention
The present invention relates generally to pharmaceutical compositions, methods and devices, and more specifically, to compositions and methods for preparing medical implants to make them more adherent to, or, more readily incorporated within a living tissue. The pharmaceutical agents and compositions are utilized to create novel drug-coated implants and medical devices which induce a fibrotic response in the surrounding tissue such that the device is effectively anchored in situ and its performance is enhanced.
2. Description of the Related Art
The clinical performance of numerous medical devices depends upon the device being effectively anchored into the surrounding tissue to provide either structural support or to facilitate scarring and healing. Effective attachment of the device into the surrounding tissue, however, is not always readily achieved. One reason for ineffective attachment is that implantable medical devices generally are composed of materials that are highly biocompatible and designed to reduce the host tissue response. These materials (e.g., stainless steel, titanium based alloys, fluoropolymers, and ceramics) typically do not provide a good substrate for host tissue attachment and ingrowth during the scarring process. As a result of poor attachment between the device and the host tissue, devices can have a tendency to migrate within the vessel or tissue in which they are implanted. The extent to which a particular type of medical device can move or migrate after implantation depends on a variety of factors including the type and design of the device, the material(s) from which the device is formed, the mechanical attributes (e.g., flexibility and ability to conform to the surrounding geometry at the implantation site), the surface properties, and the porosity of the device or device surface. The tendency of a device to loosen after implantation also depends on the type of tissue and the geometry at the treatment site, where the ability of the tissue to conform around the device generally can help to secure the device in the implantation site. Device migration can result in device failure and, depending on the type and location of the device, can lead to leakage, vessel occlusion, and/or damage to the surrounding tissue.
Numerous methods and device modifications have been proposed to secure implantable medical devices in place in the body. In one approach, the medical device is anchored mechanically to biological tissue. For example, artificial implants can be anchored to the surrounding tissues by physical and mechanical means (e.g., screws, cements and porous surfaces) or by friction. For example, mechanical attachment of a device to the site can be effected by using a fastener, such as a suture or staple. In another approach, the device includes in its design mechanical means for fastening it into the surrounding tissue. For example, the device may include metallic spikes, anchors, hooks, barbs, pins, clamps, or a flange or lip to affix the device in place (see, e.g., U.S. Pat. Nos. 4,523,592; 6,309,416; 6,302,905; and 6,152,937). A disadvantage of mechanical fasteners, however, is that they can damage the tissue or vessel wall when the device is deployed.
Other methods for preventing device migration have focused on mechanically altering the surface characteristics of the device. One such approach involves scoring or abrading the surface of the implant. The roughened surfaces promote cell, bone or tissue adhesion for better affixing of the implants in the body (see, e.g., WO 96/29030A1). Medical devices, such as implantable orthopedic devices, may be fixed to host tissue (e.g., bone) with an adhesive, such as a polymethyl methacrylate (PMMA) bone cement or a bone cement made from calcium phosphates and calcium aluminate (see, e.g., U.S. Pat. No. 6,723,334). A drawback of bone cements, however, is that over time the cemented bone-prosthesis interface can degenerate, and/or the cement itself may weaken and fail, resulting in loosening of the implant.
Chemical or biological modifications of the device surface have been used to enhance adhesion between an implantable medical device and the surrounding host tissue. For example, devices have been coated with a substance to enhance the healing process and/or adhesion of the device to the host tissue. In one approach, implantable medical devices have been developed which permit infiltration by specific desirable tissue cells. One type of tissue infiltration involves the process known as “endothelialization”, i.e., migration of endothelial cells from adjacent tissue onto or into the device surface. Methods for promoting endothelialization have included applying a porous coating to the device which allows tissue growth into the interstices of the implant surface (see, e.g., WO 96/37165A1). Other efforts at improving host tissue ingrowth capability and adhesion of the implant to host tissue include an electrically charged or ionic material (e.g., fluoropolymer) in the tissue-contacting surface of the device (see, e.g., WO 95/19796A1; J. E. Davies, in Surface Characterization of Biomaterials, B. D. Ratner, ed., pp. 219–234 (1988); and U.S. Pat. No. 5,876,743); biocompatible organic polymers (e.g., polymers substituted with carbon, sulfur or phosphorous oxyacid groups) to promote osteogenesis at the host-implant interface (see, e.g., U.S. Pat. No. 4,795,475); and coatings made from biological materials (e.g., collagen) to enhance tissue repair, growth and adaptation at the implant-tissue interface (e.g., U.S. Pat. No. 5,002,583).
The above-described approaches, however, have failed to provide a satisfactory long-term solution to the problem of device migration. Thus, there is still a need for an effective, long-lasting and biocompatible approach for anchoring implantable medical devices into or onto biological tissue.